a phase i study of gc33 in advanced or metastatic liver cancer (hepatocellular carcinoma)

Conditions: Advanced or Metastatic HCC

Summary: this phase i trial is studying the safety and best dose of gc33 in patients with advanced or metastatic liver cancer.

this is a phase i open-label dose escalation study of gc33 in patients with advanced or metastatic hcc. this study is designed to evaluate safety, tolerability, pharmacokinetics, and preliminary assessment of anti-tumor activity. enrollment will proceed until a maximum tolerated dose (mtd) and a recommended phase ii dose has been established.

Eligibility criteria:
inclusion criteria: * signed written institutional review board (irb)/ethical committee (ec) approved informed consent form * male or female ≥ 18 years old. * life expectancy ≥ 3 months. * ecog performance status of 0-1. * histologically confirmed hepatocellular carcinoma (without fibrolamellar subtype). * not a candidate for curative treatments. * child-pugh a or b. * hematological, biochemical and organ function: * ast (sgot): ≤ 5.0 × uln * alt (sgpt): ≤ 5.0 × uln * total bilirubin: ≤ 3.0 × uln * platelets: ≥ 50,000/μl * absolute neutrophil count: ≥ 1,500/μl * serum creatinine: ≤ 2.0 × uln * pt-inr: ≤ 2.0, * ability to provide a tumor tissue sample either by: * a sample obtained within 3 months prior to informed consent for hcc diagnosis. resection samples are not acceptable. * undergo a biopsy to confirm hcc diagnosis * at least one measurable lesion based on response evaluation criteria in solid tumors criteria. (extension phase) * signed written institutional review board (irb)/ethical committee (ec) approved informed consent form. * male or female ≥ 18 years old. * life expectancy ≥ 3 months. * ecog performance status of 0-1. * histologically confirmed hepatocellular carcinoma (without fibrolamellar subtype). * not a candidate for curative treatments. * child-pugh a. * hematological, biochemical and organ function: * ast (sgot): ≤ 5.0 × uln * alt (sgpt): ≤ 5.0 × uln * total bilirubin: ≤ 3.0 × uln * platelets: ≥ 50,000/μl * absolute neutrophil count: ≥ 1,500/μl * serum creatinine: ≤ 2.0 × uln * pt-inr: ≤ 2.0 * ihc confirmed gpc3-positive hcc tumor tissue. tumor tissue sample may be provided by: * a formalin fixed paraffin embedded block sample within 12 months prior to informed consent for hcc diagnosis; * unstained slides obtained within 3 months prior to informed consent for hcc diagnosis; * undergo biopsy to confirm gpc3-positive hcc. * resection samples are not acceptable. * at least one measurable lesion based on response evaluation criteria in solid tumors criteria. exclusion criteria: * child-pugh c. * pregnant or lactating women or women of child-bearing potential and men of childbearing potential not willing to use effective means of contraception. * patients known to be positive for human immunodeficiency virus infection. * active infectious diseases requiring treatment except for hepatitis b and c. * other malignancies within the last 5 years. * history of transplantation (organ, bone marrow transplantation,peripheral blood stem cell transplantation, etc.). * patients with significant concomitant disease determined by the investigator to be potentially aggravated by the investigational drug. * patients with brain metastases, other central nervous system or other psychiatric disease. * patients who received major surgery, local therapy for hcc, chemotherapy, radiotherapy, hormone-therapy, immunotherapy, or another investigational drug within 4 weeks prior to day 1. * patients who received the following treatments within 2 weeks prior to day1: * anticoagulant or thrombolytic agents for therapeutic purposes. * systemic anti-viral therapy for hepatitis c/cirrhosis. * blood transfusion * history of hypersensitivity to similar agents. * patient is unable to comply with the requirements of the protocol and/or follow-up procedures. (extension phase) * child-pugh b or c. * pregnant or lactating women or women of child-bearing potential and men of childbearing potential not willing to use effective means of contraception. * patients known to be positive for human immunodeficiency virus infection. * active infectious diseases requiring treatment except for hepatitis b and c. * other malignancies within the last 5 years. * history of transplantation (organ, bone marrow transplantation, peripheral blood stem cell transplantation, etc.). * patients with significant concomitant disease determined by the investigator to be potentially aggravated by the investigational drug. * patients with brain metastases, other central nervous system or other psychiatric disease. * patients who received major surgery, local therapy for hcc, chemotherapy, radiotherapy, hormone-therapy, immunotherapy, or another investigational drug within 4 weeks prior to day 1. * patients who received the following treatments within 2 weeks prior to day 1: * anticoagulations or thrombolytic agents for therapeutic purposes. * systemic anti-viral therapy for hepatitis c/cirrhosis. * blood transfusion * history of hypersensitivity to similar agents. * patient is unable to comply with the requirements of the protocol and/or follow-up procedures. * ihc confirmed gpc3-negative hcc tumor tissue.